Evaluation of Innovative Tools in Development of Antibiotics

NCT ID: NCT03177720

Last Updated: 2021-09-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-29
• Study Completion Date: 2021-07-31

Brief Summary

The investigators will determine the difference of pharmacokinetics of ciprofloxacin and imipenem between healthy volunteers and intensive care patients suffering from pneumonia in plasma and at the target site - lung - using bronchoalveolar lavage. As additional aspect the feasibility of combining microdosing of C14 ciprofloxacin with microdialysis, saliva sampling and bronchoalveolar lavage is studied by comparing pharmacokinetics of microdose and macrodose.

Conditions

Pneumonia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Ciprofloxacin

Half of patients and healthy volunteers are receiving ciprofloxacin, the other half imipenem.

Group Type: ACTIVE_COMPARATOR

Ciprofloxacin

Intervention Type: DRUG

Ciprofloxacin 400mg will be administered as single dose infusion over 60 minutes, imipenem/cilastatin 1000mg as single intravenous dose applicated over 60 minutes.

Imipenem

Half of patients and healthy volunteers are receiving ciprofloxacin, the other half imipenem.

Group Type: ACTIVE_COMPARATOR

Imipenem

Intervention Type: DRUG

Ciprofloxacin 400mg will be administered as single dose infusion over 60 minutes, imipenem/cilastatin 1000mg as single intravenous dose applicated over 60 minutes.

Interventions

Ciprofloxacin

Ciprofloxacin 400mg will be administered as single dose infusion over 60 minutes, imipenem/cilastatin 1000mg as single intravenous dose applicated over 60 minutes.

Intervention Type: DRUG

Imipenem

Ciprofloxacin 400mg will be administered as single dose infusion over 60 minutes, imipenem/cilastatin 1000mg as single intravenous dose applicated over 60 minutes.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Healthy male subjects aged 18 to 55 years
• Good state of health (mentally and physically)
• Body mass index within a range of 18 to 28kg/m2 inclusive.
• Non-Smoker
• A signed and dated written informed consent form.
• The subject is able to understand and willing to comply with protocol requirements and timetables, instructions and protocol-stated restrictions.
• Negative serology (human immunodeficiency virus, hepatitis B-AG and C-AB) at screening.
• Vital signs should be within the following ranges:
• Oral or tympanic temperature between 35 and 37.5°C.
• Systolic blood pressure, 90-140 mmHg.
• Diastolic blood pressure, 50-90 mmHg.
• Pulse rate, 50-90 bpm.

Exclusion Criteria

• Any acute or chronic illness or clinically relevant (Investigator's judgement) abnormality identified on the screening medical assessment, laboratory tests or ECG, unless in the opinion of the Investigator it will not interfere with the study procedures, affect the outcome of the study or compromise the safety of the subject.
• All subjects with known seizure disorder, with the exception of a febrile seizure in childhood
• Use of prescription or non-prescription drugs within 7 days or 10 times the elimination half-life (whichever is longer) prior to the first dose of study medication.
• Any intake of grapefruit juice within 1 week prior to the first dose.
• Allergies (except for mild forms of hay fever), a history of hypersensitivity reactions including psychological or neurological symptoms or signs, or anaphylactic shock following administration of any medicine.
• Allergy to or any contraindication against the active or inactive ingredients in the study medication (ciprofloxacin, imipenem, cilastatin, propofol, midazolam, remifentanil, xylocain, and sevoflurane) and radioactive labelling with 14C.
• Smoker
• Alcohol or drug abuse
• Participation in a trial with any drug within 30 days or five half-lives (whichever is longer) before the start of the study.
• Donation of blood within a period of 4 weeks prior to dosing.
• Creatinine clearance ≤70mL/min/1.73m3
• Any other reason that the Investigator considers to make the subject unsuitable to participate.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Markus Zeitlinger

Professor Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Markus Zeitlinger, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of Vienna

Locations

Medical University of Vienna

Vienna, , Austria

Countries

Austria

References

Oesterreicher Z, Eberl S, Wulkersdorfer B, Matzneller P, Eder C, van Duijn E, Vaes WHJ, Reiter B, Stimpfl T, Jager W, Nussbaumer-Proell A, Marhofer D, Marhofer P, Langer O, Zeitlinger M. Microdosing as a Potential Tool to Enhance Clinical Development of Novel Antibiotics: A Tissue and Plasma PK Feasibility Study with Ciprofloxacin. Clin Pharmacokinet. 2022 May;61(5):697-707. doi: 10.1007/s40262-021-01091-1. Epub 2022 Jan 7.

Reference Type: DERIVED

PMID: 34997559 (View on PubMed)

Other Identifiers

ELF Cipro

Identifier Type: -

Identifier Source: org_study_id